p53R2 regulates thioredoxin reductase activity through interaction with TrxR2

Biochem Biophys Res Commun. 2017 Jan 22;482(4):706-712. doi: 10.1016/j.bbrc.2016.11.099. Epub 2016 Nov 17.

Abstract

Ribonucleotide reductase small subunit p53R2 is a member of the ribonucleotide reductase family that supplies dNTPs for nuclear and mitochondrial DNA replication and repair. Here, we have identified a mitochondrial thioredoxin reductase 2 (TrxR2) as a novel p53R2-binding protein. We demonstrated a direct interaction between the two, and observed that p53R2 stimulated the enzymatic activity of TrxR in vitro. Moreover, TrxR2 activity was significantly lower in p53R2 knockdown cells, and increased when p53R2 was overexpressed, effects that were independent of p53. Furthermore, p53R2 knockdown suppressed UV-induced TrxR activity. These findings suggest that p53R2 acts as a positive regulator of TrxR2 activity in mitochondria both under normal physiological conditions and during the cellular response to DNA damage.

Keywords: Mitochondria DNA repair; Ribonucleotide reductase; Thioredoxin reductase; TrxR2; p53R2.

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • DNA Damage
  • DNA Repair
  • DNA, Mitochondrial / metabolism
  • Gene Expression Regulation, Enzymologic*
  • Genetic Vectors
  • Humans
  • Mitochondria / metabolism
  • Plasmids / metabolism
  • Protein Binding
  • RNA, Small Interfering / metabolism
  • Recombinant Proteins / metabolism
  • Ribonucleotide Reductases / metabolism*
  • Thioredoxin Reductase 2 / metabolism*
  • Ultraviolet Rays
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • DNA, Mitochondrial
  • RNA, Small Interfering
  • Recombinant Proteins
  • RRM2B protein, human
  • Ribonucleotide Reductases
  • TXNRD2 protein, human
  • Thioredoxin Reductase 2